Summary of Study ST003182

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001981. The data can be accessed directly via it's Project DOI: 10.21228/M8NQ82 This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

Study ID	ST003182
Study Title	METTL3-mediated chromatin contacts promote stress granule phase separation through metabolic reprogramming during senescence
Study Summary	METTL3 is the catalytic subunit of the methyltransferase complex, which mediates m6A modification to regulate gene expression. In addition, METTL3 regulates transcription in an enzymatic activity-independent manner by driving changes in high-order chromatin structure. However, how these functions of MTC are coordinated remains unknown. Here we show that the methyltransferase complex coordinates its enzymatic activity-dependent and independent functions to regulate cellular senescence, a state of stable cell growth arrest. Specifically, METTL3-mediated chromatin loops induce Hexokinase 2 expression through the three-dimensional chromatin organization during senescence. Elevated Hexokinase 2 expression subsequently promotes liquid-liquid phase separation, manifesting as stress granule phase separation, by driving metabolic reprogramming. This correlates with an impairment of translation of cell-cycle related mRNAs harboring polymethylated m6A sites. In summary, our results report a coordination of m6A-dependent and -independent function of the methyltransferase complex in regulating senescence through phase separation driven by metabolic reprogramming.
Institute	University of Texas MD Anderson Cancer Center
Last Name	Zhang
First Name	Rugang
Address	3SCR3.4121, 1901 East RD, Houston, TX, 77054
Email	rzhang11@mdanderson.org
Phone	832-748-6422
Submit Date	2024-04-29
Raw Data Available	Yes
Raw Data File Type(s)	raw(Thermo)
Analysis Type Detail	LC-MS
Release Date	2024-05-03
Release Version	1

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Treatment:

Treatment ID:	TR003310
Treatment Summary:	Stable isotope tracer analysis using 13C6-glucose was conducted in three biologically independent experiments for the following experimental groups: control proliferating cells (Pro), RAS-induced senescent cells via 4-OHT with control shRNA (Sen_shctrl), senescent cells with shRNA targeting HK2 (Sen_shHK2), senescent cells with shRNA targeting HK2 and rescued with wildtype Flag-HK2 (Sen_shHK2_WTHK2), and senescent cells with shRNA targeting HK2 and rescued with mutant Flag-HK2 (Sen_shHK2_MutHK2). The experiments were performed by seeding cells at a density of 3 × 10^5 cells per 6 cm dish and incubating them with 25 mM [13C6]-glucose tracer in glucose-free medium for 30 min.

Treatment ID:

TR003310

Treatment Summary:

Stable isotope tracer analysis using 13C6-glucose was conducted in three biologically independent experiments for the following experimental groups: control proliferating cells (Pro), RAS-induced senescent cells via 4-OHT with control shRNA (Sen_shctrl), senescent cells with shRNA targeting HK2 (Sen_shHK2), senescent cells with shRNA targeting HK2 and rescued with wildtype Flag-HK2 (Sen_shHK2_WTHK2), and senescent cells with shRNA targeting HK2 and rescued with mutant Flag-HK2 (Sen_shHK2_MutHK2). The experiments were performed by seeding cells at a density of 3 × 10^5 cells per 6 cm dish and incubating them with 25 mM [13C6]-glucose tracer in glucose-free medium for 30 min.